Nutrition Research and Practice 2017;11(6):487-491

ⓒ2017 The Korean Nutrition Society and the Korean Society of Community Nutrition
http://e-nrp.org

Effects of zinc supplementation on catch-up growth in children

with failure to thrive
Seul-Gi Park *, Ha-Neul Choi *, Hye-Ran Yang
1 1 2§ 1§
and Jung-Eun Yim
1
Department of Food and Nutrition, Changwon National University, 20 Changwondaehak-ro, Uichang-gu, Changwon, Gyeongnam 51140, Korea
2
Department of Pediatrics, Seoul National University Bundang Hospital, Seoul National University College of Medicine, 82 Gumi-ro, Bundang-gu, Seongnam, Gyeonggi
13620, Korea

BACKGROUND/OBJECTIVES: Although globally the numbers of children diagnosed with failure to thrive (FTT) have decreased,
FTT is still a serious pediatric problem. We aimed to investigate the effects of zinc supplementation for 6 months on growth
parameters of infants and children with FTT.
SUBJECTS/METHODS: In this retrospective study, of the 114 participants aged between 4 months and 6 years, 89 were included
in the zinc supplementation group and were provided with nutrition counseling plus an oral zinc supplement for 6 months.
The caregivers of the 25 participants in the control group received nutrition counseling alone. Medical data of these children,
including sex, age, height, weight, serum zinc level, and serum insulin-like growth factor 1 (IGF1) level were analyzed.
RESULTS: Zinc supplementation for 6 months increased weight-for-age Z-score and serum zinc levels (5.5%) in the zinc
supplementation group of underweight category children. As for stunting category, height-for-age Z-score of the participants
in the zinc supplementation group increased when compared with the baseline, and serum zinc levels increased in the normal
or mild stunting group. Serum IGF1 levels did not change significantly in any group. Thus, zinc supplementation was more
effective in children in the underweight category than those in the stunted category; this effect differed according to the
degree of the FTT.
CONCLUSION: These findings suggest that zinc supplementation may have beneficial effects for growth of infants and children
with FTT, and zinc supplementation would be required according to degree of FTT.
Nutrition Research and Practice 2017;11(6):487-491; https://doi.org/10.4162/nrp.2017.11.6.487; pISSN 1976-1457 eISSN 2005-6168

Keywords: Failure to thrive, zinc, growth, child

INTRODUCTION6)
Failure to thrive (FTT) is a state of undernutrition due to
inadequate caloric intake or caloric absorption resulting from
behavioral or psychosocial issues. FTT is a general term referring
to children whose rate of weight and height gain is much lower
than those of others at similar age [1]. FTT has been classified
as organic (underlying medical condition) or non-organic
(unknown medical condition). Non-organic FTT is the most
common type of FTT, and it includes children who are not
receiving enough food due to environmental neglect (e.g., lack
of food) or psychosocial problems [2]. However, most children
have mixed etiologies [3]. FTT is a common problem that usually
occurs during the first or second years of life and may occur
in any child [4]. Approximately 94% of children experience FTT
between 6 months and 30 months of age [5]. FTT is often
rd
defined as height and weight values falling below the 3 or
th
5 percentiles, weight being < 80% of the ideal weight for age,
or downward change in growth across 2 major growth
percentiles in the standard growth chart [6]. The World Health
Organization (WHO) uses a Z-score cutoff point of < -2 SD to
define moderate malnutrition and < -3 SD to define severe
malnutrition [7]. FTT can often be resolved through simple
interventions. Thus, primary care providers can manage children
with FTT except for those with other illnesses or constant
weight loss [8]. Cole et al. [9] reported that the most important
factor for FTT management in outpatient evaluation is obtaining
precise information on a child's food habits and energy intake.
In the US, FTT is observed in 1-5% of pediatric inpatients, about
10% of primary care patients, 15-30% of patients in urban
emergency rooms, and 15-25% of inpatients under two years
of age. The prevalence of FTT can vary depending on the
definition of the term and the participant to be observed [6,
10,11]. FTT is seen frequently in economically disadvantaged

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIP) (No.2013R1A1A3010917).
§
Corresponding Authors: Hye-Ran Yang, Tel. 82-31-787-7285, Fax. 82-31-787-4054, Email. hryang@snubh.org
Jung-Eun Yim, Tel. 82-55-213-3517, Fax. 82-55-281-7480, Email. jeyim@changwon.ac.kr
Received: June 16, 2017, Revised: July 13, 2017, Accepted: September 28, 2017
* These authors contributed equally to the study.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/)
which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
488 Effects of zinc supplement on growth retardation

rural and urban areas [12].
Zinc is a trace element that plays important roles in cell
growth and differentiation, protein and lipid metabolism, and
the immune system [13,14]. It is essential for numerous metabolic
activities, including catalysis and synthesis, degradation of
nutrients, and regulatory functions [14]. Zinc deficiency in
infants and children has been known to cause FTT and loss
of appetite [15,16]. It is reported that zinc deficiency is mainly
caused by zinc-deficient diets and food intake with high phytic
acid, which interferes with zinc absorption [17]. The staple food
in Korea is cereal grains rich in phytic acid; consequently, zinc
deficiency appears frequently [18]. Zinc deficiency symptoms
include FTT, lack of appetite, male hypogonadism in adolescents,
mental lethargy, rough skin, delayed wound healing, immune
dysfunctions, and abnormal neurosensory changes [14]. Especially,
maternal zinc deficiency during pregnancy may lead to delayed
cell growth, which may result in adverse pregnancy outcomes
for the mother and fetus [19]. The mean intake of zinc was
75.7% of reference nutrient intake among children aged 3-5
years, and serum zinc levels positively correlated with their
height and weight [20]. Therefore, deficient zinc intake may
cause FTT. Previous studies on zinc nutritional status have
included cases of adults and children with normal growth; no
studies in this regard have been conducted in children with
FTT in Korea. Therefore, this study aimed to evaluate the effects
of zinc supplementation for 6 months on growth indicators,
such as weight and height, in infants and children with FTT.
WAZ and HAZ, regardless of age. Of the total 114 participants,
89 participants who received nutrition counseling and zinc
supplementation (zinc sulfate 22 mg/day equivalent to elemental
zinc 5 mg in infancy, zinc sulfate 44 mg/day equivalent to
elemental zinc 10 mg in children) were included in the zinc
supplementation group (Zn group) [22,23]. Twenty-five parti-
cipants whose caregivers received nutrition counseling alone
were included in the control group. The trained dietician
provided 50 min of nutrition counseling, including components
of a balanced diet, roles of nutrients, and importance of food
choice. The data were analyzed based on general characteristics,
age, sex, weight, and height. To evaluate the severity of FTT,
we classified the participants into the underweight and stunting
categories. The underweight and stunting categories were
further classified into three and two groups according to their
WAZ and HAZ, respectively (Table 1). WAZ and HAZ were
calculated based on the WHO reference, using the least mean
squares method.
Statistical analysis
Statistical analyses were performed using SPSS software
version 21.0 (IBM SPSS Statistics for Windows, Version 21.0.
Armonk, NY: IBM Corp). Measured variables were presented as
mean ± SD. The difference between the control and Zn groups
was analyzed using t-test. The values for baseline and 6 months
after the zinc supplementation were compared using paired
t-test. P-value < 0.05 was considered statistically significant.

SUBJECTS AND METHODS RESULTS

Participants General characteristics

The participants’ medical records included reports on sex, The changes in the general characteristics of the control and
age, height, weight, serum zinc, and serum insulin-like growth Zn groups are summarized in Table 2. Children in both the
factor I (IGF1) levels. The study collected data from January 2012 control and Zn groups showed significant increases in their
through August 2015. Seoul National University Bundang weight and height as compared to the baseline.
Hospital’s Institutional Review Board (IRB) and Changwon
National University’s IRB approved this retrospective medical Changes in growth index
record review (IRB No. B-1603/338-110 and IRB No. 104027- Changes in growth index between 0 month and after 6
201601-HR-001, respectively). months in the control and the Zn groups are shown in Table
3. The WAZ and HAZ of children in the Zn group increased
Experimental design as compared with the baseline, whereas no significant changes
This was a retrospective study using patients’ medical records. were noted in the control group. Serum zinc levels increased
Participants aged 4 months to 6 years whose weight-for-age in the Zn group, while serum zinc levels in the control group
Z-score (WAZ) or height-for-age Z-score (HAZ) was under -1
were included. They were divided into groups according to their Table 2. General characteristics of the participants in the control and the zinc
supplementation groups at baseline and at 6-month visits
Table 1. Division of groups based on being underweight and stunted Variables Zinc (n = 89) Control (n = 25)
Category Group Mean Age (yrs) Baseline 2.4 ± 1.8 1.9 ± 1.7
Underweight -2 < WAZ < 0 Normal or marginally underweight 6 months 2.9 ± 1.8 2.4 ± 1.0
(Well-nourished or mildly malnourished) Difference 0.5 ± 0.1* 0.5 ± 0.1*
-3 < WAZ < -2 Moderately underweight Weight (kg) Baseline 10.3 ± 3.5 9.4 ± 3.5
(Moderately malnourished)
6 months 11.6 ± 3.2 10.8 ± 3.3
WAZ < -3 Severely underweight
(Severely malnourished) Difference 1.4 ± 0.9* 1.5 ± 0.7*

Stunted -2 < HAZ < 0 Normal or marginally stunt Height (cm) Baseline 82.4 ± 14.9 77.8 ± 14.6
(Well-nourished or mildly malnourished) 6 months 88.1 ± 12.9 83.8 ± 12.4
HAZ < -2 Moderately stunt Difference 5.7 ± 3.6* 6.0 ± 3.1*
(Moderately malnourished) Values are presented as mean ± SD.
WAZ, weight-for-age Z-score; HAZ, height-for-age Z-score * Significant differences within group were statistically analyzed by paired t-test
 Seul-Gi Park et al. 489

Table 3. Changes in growth indices of the control and zinc supplementation Growth index measurements in underweight
groups at baseline and 6-month visits
Changes in growth index between the baseline and after 6
Variables Zinc (n = 89) Control (n = 25) months in the control and Zn groups according to WAZ are
WAZ (Z-score) Baseline -2.0 ± 1.0 -1.7 ± 1.0 presented in Table 4. We divided the underweight category into
6 months -1.6 ± 1.0 -1.4 ± 1.0 three groups according to the WAZ. The variables were
Difference -0.4 ± 1.0* -0.3 ± 0.6 compared in each group, and the data of the control group
HAZ (Z-score) Baseline -1.5 ± 1.2 -1.5 ± 1.0 and the Zn group after 6 months were compared to the
6 months -1.2 ± 1.1 -1.2 ± 1.0 baseline data. In case of normal or mildly underweight (-2 <
Difference -0.3 ± 0.8* -0.3 ± 0.7 WAZ < 0), WAZ did not show significant difference after zinc
Zinc (μg/dL) Baseline 80.6 ± 25.5 95.8 ± 23.9† supplementation for 6 months compared to the baseline. WAZ
6 months 89.2 ± 24.3† 80.7 ± 12.5 of moderately and severely underweight children (-3 < WAZ <
Difference 8.6 ± 35.6* -15.0 ± 26.3* -2 and WAZ < -3, respectively) increased in the Zn group
IGF1 (ng/mL) Baseline 75.9 ± 58.0 68.3 ± 57.0 compared to the baseline. Serum zinc levels of normal or mildly
6 months 83.4 ± 56.2 71.7 ± 42.4 underweight children increased after 6 months in the Zn group,
Difference 7.5 ± 52.7 3.4 ± 24.5 whereas significant decreases were noted in the control group
Values are presented as mean ± SD. between the baseline and after 6 months. This indicates that
WAZ, weight-for-age Z-score; HAZ, height-for-age Z-score; IGF1, insulin-like growth
factor 1 inadequate zinc supplementation in children who are in the
* Significant differences within group were statistically analyzed by paired t-test early stage of growth retardation poses a risk of sharp decline
†
Significant differences between groups were statistically analyzed by t-test in the serum zinc concentration, which leads to poor growth
over long periods. After 6 months, serum zinc levels of the Zn
decreased when compared with the baseline. In addition, serum group significantly increased compared to baseline in children
zinc levels in the Zn group increased significantly after 6 months who were severely underweight. There were no differences in
as compared to the control group. There was no significant serum IGF1 levels between baseline and 6 months in the control
difference in serum IGF1 levels between baseline and after 6 and Zn groups according to WAZ.
months in the control and Zn groups.

Table 4. Changes in growth indices of the control group and the zinc supplementation group according to weight for age at baseline and 6-month visits
-2 < WAZ < 0 -3 < WAZ < -2 WAZ < -3
Variables
Zinc Control Zinc Control Zinc Control
WAZ Baseline -1.3 ± 0.6 -1.3 ± 0.6 -2.3 ± 0.2 -2.4 ± 0.3 -3.9 ± 0.8 -4.0 ± 1.5
6 months -1.2 ± 0.9 -1.1 ± 0.7 -2.0 ± 0.6 -2.0 ± 0.4 -2.2 ± 1.4 -3.4 ± 1.3
Difference 0.1 ± 1.0 0.2 ± 0.7 0.4 ± 0.5* 0.4 ± 0.5 1.7 ± 1.5* 0.7 ± 0.1
Zinc (μg/dL) Baseline 80.7 ± 29.2 93.2 ± 20.1† 81.9 ± 21.8 109.2 ± 34.6 75.7 ± 19.6 85.5 ± 27.6
†
6 months 93.4 ± 27.5 79.9 ± 11.5 85.4 ± 1.3 78.2 ± 16.1 82.8 ± 13.6 94.0 ± 7.1
Difference 12.7 ± 39.7* -13.2 ± 20.5* 3.5 ± 32.8 -31.0 ± 40.7 7.1 ± 22.0* 8.5 ± 20.5
IGF1 (ng/mL) Baseline 76.1 ± 55.1 62.5 ± 44.3 75.0 ± 64.1 106.0 ± 91.6 78.4 ± 55.1 27.0 ± 8.1
6 months 87.9 ± 59.2 67.7 ± 33.5 79.2 ± 53.2 104.9 ± 58.2 77.0 ± 55.8 24.7 ± 14.2
Difference 11.8 ± 58.6 5.2 ± 22.5 4.2 ± 43.9 -1.1 ± 37.2 -1.4 ± 53.9 -2.3 ± 6.1
Values are presented as mean ± SD.
WAZ, weight-for-age Z-score; HAZ, height-for-age Z-score; IGF1, insulin-like growth factor 1
* Significant differences within group were statistically analyzed by paired t-test
†
Significant differences between groups were statistically analyzed by t-test

Table 5. Changes in growth indices of the control group and the zinc supplementation group according to height for age at baseline and 6-month visits
-2 < HAZ < 0 HAZ < -2
Variables
Zinc Control Zinc Control
HAZ Baseline -1.1 ± 0.8 -1.1 ± 0.8 -3.1 ± 1.2 -2.9 ± 1.0
6 months -0.9 ± 0.7 -0.9 ± 0.9 -2.3 ± 1.3 -2.0 ± 1.3
Difference 0.2 ± 0.7* -0.4 ± 1.2 0.8 ± 0.9* 0.8 ± 0.8
Zinc (μg/dL) Baseline 80.2 ± 26.4 98.0 ± 15.3† 82.2 ± 22.6 86.8 ± 14.1
6 months 89.6 ± 26.4† 78.4 ± 13.8 88.0 ± 14.7 80.2 ± 12.4
Difference 9.4 ± 38.1* -8.3 ± 13.8* 5.8 ± 25.0 3.4 ± 14.3
IGF1 (ng/mL) Baseline 75.2 ± 53.0 66.6 ± 49.1 78.7 ± 75.3 75.3 ± 101.6
6 months 81.6 ± 53.5 72.4 ± 39.0 90.2 ± 66.6 69.1 ± 71.5
Difference 6.4 ± 56.9 -3.9 ± 74.3 11.5 ± 33.7 -6.2 ± 37.0
Values are presented as mean ± SD.
WAZ, weight-for-age Z-score; HAZ, height-for-age Z-score; IGF1, insulin-like growth factor 1
* Significant differences within group were statistically analyzed by paired t-test
†
Significant differences between groups were statistically analyzed by t-test
490 Effects of zinc supplement on growth retardation
Growth index measurements in stunting
The changes in general characteristics of low-height groups
are summarized in Table 5. In normal or mild (-2 < HAZ < 0)
and moderate (HAZ < -2) stunted cases, HAZ of the Zn group
increased compared to the baseline. In normal or mild stunting,
serum zinc levels of the Zn group significantly increased after
6 months compared to the baseline, whereas serum zinc levels
of the control group significantly decreased. These results were
similar to those of the normal or mild underweight children
in the underweight group. Thus, inadequate zinc supplementation
in children in the early stages of growth failure may lead to
decreased serum zinc concentration resulting in severe growth
failure. Serum IGF1 levels at baseline and after 6 months of
zinc supplementation were not significantly different between
the control and Zn groups.
DISCUSSION
The prevalence of stunting and underweight in children has
decreased worldwide, from 40% in 1990 to 26% in 2011 and
25% in 1990 to 16% in 2015, respectively [23]. However, FTT
is still a serious problem in infants and children. Daniel et al.
[5] investigated the causes of FTT in a children’s hospital. They
found that these children had nutritional deficiencies (51.5%)
and short stature due to being small for gestational age,
constitutional or familial short stature (28.9%), or gastrointes-
tinal disorders (16%). Although FTT was associated with various
factors, nutritional supply and absorption were prominent
factors associated with FTT. Therefore, intensive nutrition
therapy may help with catch-up growth. Most patients with FTT
can be treated with nutritional support and dietary corrections,
and more aggressive treatment is needed if they do not
respond to treatment [3].
We investigated the effects of zinc supplementation for 6
months on catch-up growth in children with FTT. During the
experimental period, participants in the Zn group were given
10 mg of zinc daily. Zinc concentration was determined based
on previous studies [21,22]. After 6 months, the effects on
weight, height, WAZ, HAZ, serum zinc, and IGF1 levels in
participants were studied.
The WAZ and HAZ were significantly increased by zinc
supplementation in the normal or mild underweight and
stunting groups, respectively. In normal or mild underweight
and stunting, serum zinc levels of the Zn group significantly
increased after 6 months compared to baseline. In addition,
serum zinc levels of the Zn group significantly increased
compared to the control group. All growth parameters of the
Zn group in moderate stunting showed no significant changes
after 6 months compared to the baseline, except for HAZ. Thus,
zinc supplementation was more effective for underweight
children than stunting children, and it may play an important
role in catch-up growth by significantly increasing serum zinc
concentrations at the early stages of growth retardation.
It was reported that consumption of zinc (50 mg/day for
2-months) improved secretion of growth hormone in children
aged 3.7-16.2 years. In addition, zinc supplementation was more
effective in children with low BMI than in those with normal
BMI [24]. Thus, effects of zinc supplementation differed depending
on the characteristics of children with FTT. Unlike WAZ, HAZ
is known as an indicator of chronic malnutrition [25]. The
catch-up growth in height is slower than catch-up growth in
weight, hence, constant nutritional support is needed until HAZ
reaches its normal value [26]. Our study also showed that the
stunting group had less benefit from zinc supplementation than
the underweight group. However, it may be necessary to
conduct a long-term experiment with different concentrations
of zinc supplementation depending on the degree of FTT.
Zinc is the second most abundant micronutrient in the body
and plays an important role not only in physical growth, but
also as a cofactor for enzymes required for DNA synthesis, brain
development, cell membrane fluidity and stability, bone
formation, and wound healing [27]. It is necessary to maintain
a consistent intake because zinc is not stored in the body [28].
The normal range of serum zinc levels is 70-120 μg/dL [29].
Zinc homeostasis is well maintained in the body. Even when
there is a serious deficit in zinc intake, blood zinc levels do
not alter significantly. Thus, it is possible that zinc deficit exists
even when blood zinc levels appear to be within the normal
range [30]. Our study showed that serum zinc levels increased
in the Zn group, while serum zinc levels in the control group
decreased compared with baseline. Therefore, it is important
to diagnose growth retardation and zinc deficiency early using
various indicators, and to start zinc supplementation at an
appropriate time to prevent long-term zinc deficiency. In addition,
to accurately investigate zinc status in the body, other samples
in addition to blood should be collected and examined.
IGF1 is mostly made by the liver under the control of pituitary
growth hormone (GH). IGF1 modulates GH secretion through
a negative feedback mechanism. GH/IGF1 signal pathway is
essential for growth in infants and children [31]. There have been
many studies that associate zinc with IGF1 levels [32,21,33]. Zinc
deficiency significantly reduced serum IGF1 concentrations.
Furthermore, the decrease in serum IGF1 concentrations was
associated with decreased IGF1 gene expression in the liver of
rats with zinc deficiency [32]. Oral administration of zinc (10
mg) for 3 months increased consumption of macronutrients and
plasma IGF1 levels in children aged 8-9 years [21]. Cossack [33]
reported that poor zinc status has been associated with low
circulating IGF1 levels despite adequate caloric intake in
humans. Thus, IGF1 is zinc-dependent and could be used as
an indicator for diagnosing zinc deficiency. Unlike the previous
studies, our study showed that zinc supplementation did not
affect serum IGF1 levels. This result may have been due to the
different age range of participants or the normal range of serum
zinc and IGF1 levels in participants.
This study presented that zinc supplementation for 6 months
in infants and children with FTT increased growth and serum
zinc levels significantly in the Zn group of mild low weight and
height participants compared with the control group. In
addition, the effect of zinc supplementation differed according
to FTT severity, suggesting that zinc supplementation should
be performed according to the stage of FTT. However, this study
has some limitations. This was a retrospective study, using
restricted medical records. Additionally, zinc intake and toxicity
were not studied. We suggest that prospective studies should
be conducted to investigate effects of zinc supplementation on
 Seul-Gi Park et al.
catch-up growth in infants and children with FTT and low serum
zinc levels.
In conclusion, zinc supplementation may be beneficial for
growth in infants and children with FTT, and supplementation
based on degree of FTT is suggested.
CONFLICT OF INTEREST
The authors declare no potential conflicts of interests.
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